Cinnamon Aqueous Extract Attenuates Diclofenac Sodium and Oxytetracycline Mediated Hepato-Renal Toxicity and Modulates Oxidative Stress, Cell Apoptosis, and Inflammation in Male Albino Rats

Among commonly consumed anti-inflammatory and antimicrobial drugs are diclofenac sodium (DFS) and oxytetracycline (OTC), especially in developing countries because they are highly effective and cheap. However, the concomitant administration of anti-inflammatory drugs with antibiotics may exaggerate massive toxic effects on many organs. Cinnamon (Cinnamomum zeylanicum, Cin) is considered one of the most broadly utilized plants with various antioxidant and anti-inflammatory actions. This study aimed to evaluate the possible protective effects of cinnamon aqueous extract (Cin) against DFS and OTC hepato-renal toxicity. Eight groups (8/group) of adult male albino rats were treated orally for 15 days with physiological saline (control), Cin aqueous extract (300 mg/kg b.w.), OTC (200 mg/kg b.w.), single dose of DFS at the 14th day (100 mg/kg b.w.), DFS + OTC, Cin + DFS, Cin + OTC, and Cin + DFS + OTC. The administration of DFS and/or OTC significantly increased (p < 0.05) the serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, urea, creatinine, and uric acid. Serum levels of pro-inflammatory cytokines, as well as hepatic and renal malondialdehyde and nitric oxide metabolites, were also raised following DFS and OTC administration. Meanwhile, the activities of reduced glutathione, superoxide dismutase, and catalase in liver and kidney were significantly suppressed in DFS, OTC, and DFS + OTC treated rats. Moreover, hepatic and renal tissue sections from these rats exhibited overexpression of caspase-3 and cyclooxygenase-II on immunohistochemical investigation. The administration of Cin aqueous extract ameliorated the aforementioned deteriorations caused by DFS, OTC, and their combination. Conclusively, Cin is a promising protective plant extract capable of attenuating the oxidative damage, apoptosis, and inflammation induced by DFS and OTC either alone or combined, on hepatic and renal tissues.